Acne is a chronic inflammatory disorder of the pilosebaceous follicles, particularly in the face and neck region, occurring most commonly in adolescence between the ages of about 14 to about 19. Acne involves increased sebum secretion, hyperkeratinization in the infrainfundibulum of the follicular duct, increased microbial colonization and inflammation (Straiss, (J. S., J. Dermatol. Treat., 1:3-6 (1989)). Various methods for the treatment of acne and other sebaceous glands' inflammation have been proposed, ranging from special diets, prevention of contact of the skin by known acneignic agents (e.g., low grade cosmetics), use of endocrine preparations containing progesterone or estrogen, and others, most of which have not proved to be effective. Additionally, it has also been proposed to use antiseptic, antibacterial and wide-spectrum antibiotic compounds in both topical and systemic application.
All hitherto used anti-acne agents were effective in suppressing the development of microbial population, keratinization and comedo formation in the sebaceous glands. However, only few of the anti-acne agents hitherto used were effective in the reduction of the sebum excretion rate (Gollnick, H., J. Dermatol. Treat. 1:S23-S28 (1990) and none of the agents was useful in affecting lipid biosynthesis in the pilosebaceous unit.
Xerosis in the "dry" rough quality of skin, particularly old skin, which origin is quite controvertical, although this surface irregularity may also be attributed simply to slower transit of corneocytes through the stratum corncum allowing accumulation of damage in situ.
The term "Ichtyosiform dermatoses", also at times termed hereinafter as "Ichthyosis", concerns a heterogenous group of heriditary disorders, allow which are characterized by the accumulation of large amounts of scale on the cutaneous surface.
Rosacea was originally termed "acne rosacea" which is an inappropriate term that still persists. Papules and papulopustules occur in the central region of the face against a vivid erythematous background with telangiectases. Later, there may occur diffuse hyperplasia of connective tissue with enlarged sebaceous glands. The disease evolves in stages. The early signs are recurrent episodes of blushing that finally become persistent dark red erythema, particularly on the nose and cheeks, often before the age of twenty. These persons are the so-called flushers and blushers. Rosacea is common in the third and fourth decades and peaks between the ages of 40 to 50 years. In the worst cases, disfiguring hypertrophy, particularly of the nose which is termed "rhinophyma" may develop after many years.
Allergic contact dermatitis is usually evident by acute erruptions which are characterized by macular erytherma and papules, vesicles or bullae, which occur after contact with the allergens. At its initiation, contact dermitis usually involves the cutaneous site of principal exposure, i.e. the region which comes into direct contact with the allergen. However, if it evolves, it can spread to other more distant sites, either by inadvertent contact or under certain circumstances by auto-sensitization.
Atopic dermatitis also termed "atopic eczema" is a chronically relapsing skin disorder that arises most commonly during infancy childhood or adolescence. The main syndrome in atopic dermatitis is the characteristic "itch" which causes scratching, prurigo papules, lichenification and eczematous lesions.
Seborrheic dermatitis is common and usually easily recognized. It affects babies and adults and is often associated with increased sebum production (seborrhea) of the scalp and the sebaceous folicle-rich areas of the face and trunk. The affected skin is pink, edematous, and covered with yellow-brown scales and crusts. The disease has a wide range from mild to severe including psoriasi-form patterns and erythroderma.
Isoprenoid groups such as cholesterol, squalene and cholesterylesters are synthesized via the mevalonate pathway (Goldstein, J. L., Brown, M. S., Nature, 34B, 425 (1990)), wherein the end-product is cholesterol. One of the key enzymes which regulate the production of mevalonate, the precursor of the above isoprenoid groups, is the 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase. Inhibitors of this enzyme inhibit the synthesis of cholesterol and are thus used as antihypercholesterolemic medicaments for the treatment of arteriosclerosis, hyperlipemia and related diseases. Example of such an inhibitor is Lovastatin (Merck Index 5460, U.S. Pat. No. 4,231,938), Fluvastatin (XU 62-320, EP 0114 027), Paravastatin (Merck Index 7712, U.S. Pat. No. 4346,227), Simvastatin (Merck Index 8491, U.S. Pat. No. 4,444,784); Atorvastatin (CI-981), Cerivastatin (BAY W6228) and Crilvastatin (Pan Medica, Carros France) (all mentioned in Negre-Aminou et al., Biochimica et Biophysica Acta 1345:259-268 (1997)). Pharmaceutical compositions comprising this inhibitor of HMC-CoA reductase are given orally or parenterally to patients suffering from arteriosclerosis or hyperlipemia.